1. Field of the Invention
The present invention relates to a tamper proof system for the delivery of narcotics to a subject. In particular, the present invention relates to a composition containing an agonist, an antagonist, and an antagonist removal component capable of removing the antagonist component from the gastrointestinal tract of the subject.
2. Background Information
Narcotic medications such as those described in U.S. Pat. No. 5,958,452, including but not limited to all drugs classified as opiates or opioids, are the most effective pain relievers available and have long been known and prescribed by the medical community for their unsurpassed analgesic effect in the human body. At the same time, however, patients taking prescribed dosages of narcotic medications exhibit a tendency to develop tolerance to and physical dependence on the prescribed medication, leading to the potential for abuse. Additionally, a distinct minority in the population has utilized and abused narcotics in an effort to attain and sustain a euphoric state that has no medical purpose. Narcotics offer fertile ground for such experimentation and subsequent addiction.
U.S. law closely regulates the availability and use of narcotics for medicinal purposes in an attempt to prevent abuse and tampering. Under the Comprehensive Drug Abuse Prevention and Control Act of 1971, specific requirements are established for record-keeping by pharmacists, formats for prescription writing, and maximum amounts of applicable drugs that can be legally dispensed. The Act further restricts prescriptions for Schedule II drugs, which include narcotics, mandating that such drug orders may not be filled or refilled without a written format. Federal law further mandates a strict accounting system to track all hospital and pharmacy dispensing of narcotics.
These barriers have no doubt restricted the opportunity for tampering and abuse by individuals of narcotics. Additionally, government-sponsored programs to aid addicted individuals (principally methadone programs) have a long history of use and some record of success. Nevertheless the problem persists of widespread and serious illegal use and abuse of narcotics manufactured for medicinal purposes.
In the past, efforts to control abuse of narcotics have included the development of drugs that incorporate an opioid antagonist, which is designed to be orally inactive and to block the analgesic effects of the opioid agonist if first dissolved and then administered parenterally. Such dosages are, however, still vulnerable to misuse and abuse by patients that resort to oral administration of multiple doses simultaneously. In addition, such dosages do not address the problem of abuse by means of nasopharyngeal routes of administration, i.e. “snorting” the drug.
Others have attempted to target and eliminate the illicit “street” extraction potential of the opioid constituent in agonist/antagonist substances by directly combining the opioid agonist and antagonist together in a unit structure. The extraction of the opioid constituent requires multiple step extraction methods not generally available to an unsophisticated street user.
While this approach may lower the tampering and abuse potential, it presents unique drawbacks. This approach predictably is forced to compromise analgesic action. Peer-reviewed literature finds that, in clinical trials, agonists acting alone yield better clinical results than comparable agonist/antagonist formulations. Studies have also shown that such combinations of agonist with antagonist create a potential for limited success in pain management. Certain patients may benefit while others experience results ranging from less efficacious pain management to limited or no therapeutic relief to slight or even profound aversion responses. Additionally, because this approach delivers a dosage of 80% agonist/10% antagonist, it is possible that the antagonist will ultimately bind all opiate receptors, completely nullifying and obstructing further delivery of intended agonist agents in protracted use by patient populations. Such a “point of saturation” represents a serious potential disadvantage to patients requiring prolonged use in cases of chronic conditions.
Several approaches which attempt to reduce tampering and prevent abuse of various opiate/opioid dosage forms have been described. These include U.S. Pat. Nos. 3,493,657, 3,773,955, 4,457,933, 4,582,835, and 6,228,863, each of which addresses one or a combination of problems present in the art. Unfortunately, the general problem of abuse of narcotic medications persists and evidence demonstrates that this problem is growing.
Several U.S. Patents have described technologies related to this invention. These include U.S. Pat. Nos. 6,214,379 and 6,020,002, which describe immediate-acting and time-released dosage forms; U.S. Pat. No. 5,958,452, which discloses a multiparticulate composition for pain management; and U.S. Pat. Nos. 5,609,886 and 6,066,339, which describe multi-component formulations. Each patent is herein incorporated by reference in its entirety. In each of these patents the selection of the components reflects the relevant chemical's ability to act effectively in a particular route of administration, as described in U.S. Pat. Nos. 5,512,587 and 5,783,583, while possessing sufficient action per dosage to independently neutralize the entire analgesic or euphoric potential of the agonist agent. However, none of these approaches provides a composition in which tampering potential can be reduced without comprising analgesic action.
U.S. Pat. Nos. 6,261,599 and 6,335,033, U.S. patent application Ser. No. 2002/0010127, and patent publication WO 01/58451 describe methods for manufacturing opioid formulations designed to release a therapeutically active agent over a period of time. However, none of these approaches provides a composition that includes an agent for the removal of an antagonist component.
There is therefore a need in the art for a composition containing an agonist and an antagonist and having reduced tampering potential while maintaining an effective analgesic action.